This research project involves computational studies of the biologically relevant chemistry of NO and derivatives using state-of-the-art theoretical methods. The principal goals of the research are to answer the following questions: 1. What chemistry occurs when N-hydroxyarginine, an intermediate in NO synthesis by NO synthase, is released from the enzyme? 2. What is the mechanism of decomposition of OONO-, as well as radical and nitration chemistry of this species, upon protonation or reactions with CO2 or ketones. Are the HO ONO and NO2 CO3- radical pairs in water involved? Can the "sticky cage" account for the peculiar properties which have led to postulation of an excited intermediate HOONO? 3. How are nitrosothiols formed from thiols, and how is NO released? What controls the stabilities of nitrosothiols and how NO, NO-, and NO+ are released or transferred under specific conditions? Can a catalog of rates and thermodynamics of reactions involving NO and its ions be created? Collaborations with experimental groups provide challenging problems and stringent tests of the results of theory.